This is a new application from Dr. Leonard Freedman who proposes to investigate the role of vitamin D3 inducible genes in cell differentiation. Specifically, a select set of genes that are under direct transcriptional induction by the vitamin D receptor (VDR) will be characterized for their ability to induce differentiation of the human myeloid leukemic cell U937 to the monocyte/macrophage pathway. Four specific aims are proposed: 1) identify which of the vitamin D3 inducible genes in U937 cells are direct targets for the VDR and characterize a select set of these genes for their ability to induce U937 differentiation; 2) examine whether the VDR target genes characterized under the first aim cooperate to synergize U937 differentiation in the absence of the hormone, 3) examine the generality of the differentiation inducing effects of the VDR target genes in other myeloid and in nonmyeloid cells, 4) explore the mechanism for the transcriptional activation of the VDR target genes.